The sixth edition of the AJCC Cancer Staging Manual contains some of the most extensive and significant revisions that have ever been made in the breast cancer staging system. The principal changes are related to the size, number, location, and method of detection of regional metastases to the lymph nodes. Some changes are related to the growing use of new technology (eg, sentinel lymph node biopsy, immunohistochemical staining, reverse transcriptase-polymerase chain reaction), whereas others are amendments of prior staging criteria, reflecting recent clinical evidence or widespread clinical consensus. Available data did not support the addition of new prognostic indicators such as histologic tumor grade to the tumor-node-metastasis system at this time. Future developments in determining breast cancer prognosis will most likely incorporate new approaches to identifying the genetic fingerprint of individual tumors.